In silico investigation of a new 4-hydroxyquinolone analogue as Anaplastic Lymphoma Kinase (ALK) inhibitor: molecular docking and ADMET prediction

Cancer is one of the most alerting diseases menacing global health; therefore, developing cancer therapies is a priority. Among the developed cancer treatments; the targeted therapy, in which a small molecule targets specific proteins that help the cancer growing such as tyrosine kinases.

In the search for new potential drug-candidates acting as anticancer agents, we were interested in a small molecule derived from 4-hydroxy-2-quinolone newly synthesized from the condensation of a β-enaminone and diethylmalonate under microwave irradiation. This compound was subjected to an in silico study in order to investigate their potentiality to act against lung cancer through inhibiting a tyrosine kinase; Anaplastic Lymphoma Kinase (ALK). A docking simulation was performed in the active pocket of the human ALK complexed with a commercialized anticancer agent; Entrectinib (Pdb: 5FTO) using Schrodinger suite. The studied derivative showed a good stability inside the active site with an estimated docking score equal to -8.054 kcal.mol^-1. In addition, significant interactions, similar to those formed by the co-crystallized ligand, were present in the studied compound counting hydrogen bonds with Met1199 and Glu1197 as well as hydrophobic contacts with residues in the cavity of the ALK. Keeping in mind that the pharmacokinetic properties and the toxicity of a drug-candidate are very important factors in conceiving a safe admissible therapeutic substance, we carried out an ADMET prediction to the studied molecules using SwissADME, MolSoft, and ProTox-II which gave promising results.